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浙江大学学报(医学版)  2017, Vol. 46 Issue (2): 173-178    DOI: 10.3785/j.issn.1008-9292.2017.04.09
原著     
卵巢上皮性癌组织中DNAJB11的表达及临床意义
姚国荣1,3(),傅云峰1,李艳丽1,周彩云2,吕卫国1,*()
1. 浙江大学医学院附属妇产科医院肿瘤科, 浙江 杭州 310006
2. 浙江大学医学院附属妇产科医院病理科, 浙江 杭州 310006
3. 湖州市中心医院妇产科, 浙江 湖州 313000
Expression and clinical significance of DNAJB11 in epithelial ovarian cancer
YAO Guorong1,3(),FU Yunfeng1,LI Yanli1,ZHOU Caiyun2,LV Weiguo1,*()
1. Department of Gynecologic Oncology, Women's Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang 310006, China
2. Department of Pathology, Women's Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang 310006, China
3. Department of Obstetrics and Gynecology, Huzhou Central Hospital, Huzhou, Zhejiang 313000, China
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摘要:

目的:探讨DNAJB11蛋白在卵巢上皮性癌组织中表达及其临床价值。方法:采用免疫组织化学EnVision法检测105份卵巢上皮性癌的石蜡包埋组织DNAJB11蛋白的表达情况,并与23份正常卵巢组织、17份卵巢良性肿瘤组织、13份卵巢交界性肿瘤组织对比,用χ2检验分析其与临床病理特征的关系,用Kaplan-Meier法及COX比例风险回归模型分析其与患者生存预后的关系。结果:DNAJB11蛋白在正常卵巢组织及卵巢良性肿瘤中几乎不表达,在交界性肿瘤组织中阳性率为7.7%,在卵巢上皮性癌组织中阳性率为78.1%,卵巢上皮性癌组织中DNAJB11表达均高于其余各卵巢病变和正常卵巢组织(均P<0.01)。在细胞分化程度为G2~G3、临床分期为Ⅲ~Ⅳ期、组织学类型为浆液性、术前外周血CA125水平大于500 IU/L的卵巢上皮性癌患者中,卵巢上皮组织DNAJB11蛋白表达均高于细胞分化程度为G1、临床分期为Ⅰ~Ⅱ期、组织学类型为非浆液性癌和血CA125水平不超过500 IU/L的患者(均P<0.05)。Kaplan-Meier生存曲线显示,DNAJB11强阳性表达与上皮性卵巢癌患者的总生存预后及无瘤生存预后相关(P<0.01);多因素分析结果显示,DNAJB11蛋白强阳性表达是卵巢上皮性癌无瘤生存及总生存的独立预后因素。结论:DNAJB11蛋白可能在卵巢上皮性癌发生发展过程中起重要作用;卵巢上皮组织DNAJB11蛋白强阳性表达是卵巢上皮性癌患者的独立预后因素。

关键词: 卵巢肿瘤/病理学蛋白质组学免疫组织化学预后    
Abstract:

Objective: To study the expression of DNAJB11 protein in epithelial ovarian cancer tissues and its clinical significance. Methods: Immunohistochemistry was used to examine DNAJB11 expressions in 105 tissue specimens of ovarian epithelial carcinoma, 23 normal ovarian tissues, 17 tissues of benign tumor, and 13 tissues of of borderline tumor. The correlations between protein expression and clinicopathological factors were analyzed by Chi square test.The correlations between protein expression and survival were analyzed by Kaplan-Meier and Cox regression. Results: Positive expression of DNAJB11 protein was observed in 0.0% in normal ovary and benign tumor, 7.69% in borderline tumor, and 78.10% in epithelial ovarian cancer, respectively. Positive expression of DNAJB11 protein was significantly higher than the rest of the ovarian tissues and normal ovarian tissues (P<0.001).Higher expression of DNAJB11 was more prevalent in tissues from patients with advanced FIGO stages, high serum CA125, poor histological differentiation, and serous cancer. Kaplan-Meier curves revealed that higher expression of DNAJB11 was significantly associated with poor disease-free survival and overall survival.Multivariate survival analysis revealed that strong positive expression of DNAJB11 was an independent prognostic factor for disease-free survival and overall survival. Conclusion: DNAJB11 may play a role in tumorigenesis and progression of epithelial ovarian cancer.Strong positive expression of DNAJB11 was an independent prognostic factor in epithelial ovarian cancer.

Key words: Ovarian neoplasms/pathology    Proteomics    Immunohistochemistry    Prognosis
收稿日期: 2016-09-30 出版日期: 2017-10-31
基金资助: 高等学校博士学科点专项科研基金(20110101120142);国家高技术研究发展计划(863计划)(2012AA02A507);浙江省卫生高层次创新人才培养工程
通讯作者: 吕卫国     E-mail: 110790470@qq.com;lbwg@zju.edu.cn
作者简介: 姚国荣(1980—),男,硕士研究生,主治医师,主要从事妇科肿瘤研究;E-mail: 110790470@qq.com;http://orcid.org/0000-0001-5514-5125
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引用本文:

姚国荣,傅云峰,李艳丽,周彩云,吕卫国. 卵巢上皮性癌组织中DNAJB11的表达及临床意义[J]. 浙江大学学报(医学版), 2017, 46(2): 173-178.

YAO Guorong,FU Yunfeng,LI Yanli,ZHOU Caiyun,LV Weiguo. Expression and clinical significance of DNAJB11 in epithelial ovarian cancer. J Zhejiang Univ (Med Sci), 2017, 46(2): 173-178.

链接本文:

http://www.zjujournals.com/xueshu/med/CN/10.3785/j.issn.1008-9292.2017.04.09        http://www.zjujournals.com/xueshu/med/CN/Y2017/V46/I2/173

[n(%)]
组织类型 n 阴性 阳性 强阳性
正常卵巢组织 23 23 0(0) 0(0)
卵巢良性肿瘤 17 17 0(0) 0(0)
卵巢交界性肿瘤 13 12 1(7.7) 0(0)
卵巢上皮性癌 105 23 48(45.7) 34(32.4)
表 1  不同卵巢病变组织中DNAJB11蛋白表达的比较
图 1  上皮性卵巢组织DNAJB11蛋白免疫组织化学检测结果
特征 n 阴性 阳性 强阳性 χ2 P
 年龄(岁)
   ≤50 52 11 26 15 0.838 0.658
    > 50 53 12 22 19
 临床分期
   Ⅰ-Ⅱ 40 18 15 7 21.107 0.000
   Ⅲ-Ⅳ 65 5 33 27
 残余灶直径(cm)
   ≤1 75 20 32 23 3.489 0.175
    > 1 30 3 16 11
 细胞分化程度
   G1 14 7 5 2 7.808 0.020
   G2-3 91 16 43 32
 组织学类型
   浆液性 60 8 32 20 6.513 0.039
   非浆液性 45 15 16 14
 外周血CA125水平(IU/L)
   ≤500 60 18 27 15 6.559 0.038
    > 500 45 5 21 19
 化疗敏感性
   敏感 77 19 35 23 1.578 0.454
   耐药 28 4 13 11
表 2  不同临床病理特征患者卵巢上皮性癌组织表达DNAJB11比较
图 2  卵巢上皮性癌组织中不同DNAJB11蛋白表达患者的总生存曲线比较
图 3  卵巢上皮性癌组织中不同DNAJB11蛋白表达患者的无瘤生存曲线比较
因素 总生存 无瘤生存
HR(95% CI) P HR(95% CI) P
   年龄 1.582(0.875~2.861) 0.129 1.417(0.855~2.348) 0.176
   病理类型 1.037(0.547~1.967) 0.911 1.207(0.682~2.134) 0.519
   组织分化程度 1.453(0.403~5.234) 0.568 1.930(0.688~5.413) 0.211
   临床分期 3.515(1.470~8.404) 0.005 1.937(0.920~4.080) 0.082
   血CA125水平 1.345(0.669~2.702) 0.405 1.351(0.739~2.467) 0.328
   残余灶大小 1.116(0.571~2.181) 0.749 1.113(0.616~2.012) 0.723
   化疗疗程 1.011(0.509~2.007) 0.976 1.226(0.660~2.275) 0.519
   化疗敏感性 3.101(1.635~5.880) 0.001 2.245(1.266~3.982) 0.006
   DNAJB11阳性 1.035(0.357~2.998) 0.950 1.372(0.569~3.307) 0.482
   DNAJB11强阳性 2.168(1.059~4.439) 0.034 2.447(1.312~4.563) 0.005
表 3  影响卵巢上皮性癌患者预后因素的COX单因素生存分析结果
因素 总生存 无瘤生存
HR(95% CI) P HR(95% CI) P
  临床分期 4.113(1.828~9.252) 0.001 2.560(1.321~4.960) 0.004
  化疗敏感性 3.454(1.966~6.068) <0.001 2.192(1.319~3.642) 0.002
  DNAJB11阳性 0.913(0.330~2.525) 0.861 1.333(0.573~3.101) 0.504
  DNAJB11强阳性 1.971(1.010~3.847) 0.047 2.259(1.244~4.102) 0.007
表 4  影响卵巢上皮性癌患者预后因素的COX多因素生存分析结果
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